目的 評(píng)價(jià)抗HER2 人源化抗體的急性毒性。方法 將食蟹猴隨機(jī)分為4 組,包括溶媒對(duì)照和抗HER2 人源化抗體75、150 和250 mg/kg 組,單次iv 溶媒對(duì)照組或供試品,進(jìn)行各項(xiàng)毒理學(xué)指標(biāo)檢測(cè)。結(jié)果 給藥后各組動(dòng)物臨床癥狀、體質(zhì)量、攝食量、體溫、心電圖、血壓和血液學(xué)檢測(cè)均未見(jiàn)明顯異常;血清生化結(jié)果顯示,150 mg/kg 組與250 mg/kg 組動(dòng)物給藥后血清IgG 水平出現(xiàn)一過(guò)性增加;各組動(dòng)物均未見(jiàn)大體病理學(xué)改變。結(jié)論 食蟹猴單次iv 抗HER2 單抗,總體上動(dòng)物具有良好的耐受性,最大耐受劑量可達(dá)250 mg/kg,這些結(jié)果為進(jìn)一步臨床前評(píng)價(jià)抗HER2 人源化單克隆抗體的安全性奠定了基礎(chǔ)。

Objective To evaluate the single dose toxicity of a humanized anti-HER2 monoclonal antibody. Methods Cynomolgus monkeys were randomly divided into four groups: vehicle control, 75, 150, and 250 mg/kg. All animals were iv administered with a single-dose vehicle control or test article. Then a series of toxicological parameters were determined. Results Following a single iv injection with anti-HER2 monoclonal antibody, there were not obvious abnormalities in clinical symptom, food consumption, weight, temperature, electrocardiogram, blood pressure, and hematology analysis for all article-treated groups. A transient increase of serum IgG was observed in 150 and 250 mg/kg dosage groups. No macro-pathological change was found in all animals. Conclusion Single iv injection with anti-HER2 monoclonal antibody was well tolerated in cynomolgus monkeys. The maximum tolerated dose of anti-HER2 monoclonal antibody is greater than that of 250 mg/kg. These results will facilitate further preclinical safety studies of humanized anti-HER2 monoclonal antibody.

十二五“重大新藥創(chuàng)制”科技重大專項(xiàng)(2012ZX09302001)